EFFECT OF POTASSIUM AND VALINOMYCIN ON INSULIN AND GLUCAGON-SECRETION IN PERFUSED RAT PANCREAS

We examined the response of the α and β-cells of the perfused rat pancreas to an elevation of potassium ion concentration and to the potassium ionophore, valinomycin (1 × 10-6< M). Elevation of potassium from a baseline concentration of 5.8 mM to 11.3, 18.3, and 53.3 mM caused a biphasic release of immunoreactive insulin characterized by a spiked first phase and a low sustained second phase and a spiked release of immunoreactive glucagon followed by a very low sustained secretion that ended with the termination of the stimulation. The second phase of potassium-stimulated insulin release increased in the presence of basal glucose (3.3 mM). Sequential higher concentrations of potassium caused a dose-response increase in both phases of insulin release, but did not increase glucagon secretion. Valinomycin inhibited the insulin secretion caused by potassium, arginine, and glucose and the glucagon secretion caused by potassium and arginine. Potassium, when applied on the second phase of arginine-stimulated insulin and glucagon release, enhanced the secretion of insulin but caused a dramatic inhibition of glucagon that did not correlate directly with insulin release and which may possibly result from the entrance of an excessive amount of calcium into the islet cells. The secretion caused by potassium has been attributed to its depolarizing qualities. If the principal effect of valinomycin is a result of its postulated hyperpolarization of the islet cells, it seems that the electrical behavior of the α and β-cells with regard to secretion is similar; depolarization enhances secretion and hyperpolarization inhibits it. Finally, the established inhibition of glucagon secretion by glucose must be induced by a mechanism other than depolarization. © 1978 by The Endocrine Society.